The role of angiotensin II (AII) located within the brain and/or in the pituitary in the regulation of LH secretion will be investigated in the rat. AII could affect LH secretion via: (1) an action of the peptide within brain tissue to modify neurotransmitter and/or luteinizing hormone releasing hormone (LHRH) secretion, (2) an action of brain AII directly upon LH secretion at the level of the pituitary by release from the median eminence and transit along the portal vasculature; or (3) an action of AII manufactured within the pituitary to locally modulate LH release. The experiments proposed in this grant are designed to investigate these possibilities through the use of various methodologies. (1) direct perifusion of pituitary tissue with AII or with AII receptor blockers to determine their effects upon basal and LHRH stimulated LH secretion; (2) identification of AII in anterior pituitary tissue by radioimmunoassay after chromatography and subsequent manipulation of peptide concentrations by ovariectomy, hormone replacement, or inhibitors or renin or converting enzyme activity. Parellel immunocytochemistry experiments will detemine whether the AII-like immunoreactivity found in gonadotrops is modified by such manipulations; (3) in vivo investigation of central or peripheral AII involvement of the proestrous LH surge through the use of AII receptor blockers or inhibitors of renin or converting enzyme activity, and in vivo investigation of possible mediators of brain AII effects upon LH secretion by (4) manipulation of central neurotransmitter systems; or (5) lesions of putative brain sites of action. These experiments will provide information on the mechanism and site of action whereby AII in the brain and/or in the pituitary modulate LH secretion. This will be the first comprehensive investigation of the effects of AII, a peptide long been known to influence cardiovascular control and fluid balance on LH secretion.